Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease

Tatiana Foroud, S. K. Uniacke, L. Liu, N. Pankratz, A. Rudolph, C. Halter, C. Shults, K. Marder, P. M. Conneally, W. C. Nichols, Lawrence Golbe, William Koller, Kelly Lyons, Frederick Marshall, David Oakes, Aileen Shinaman, Eric Siemers, Joanne Wojcieszek, Joann Belden, Julie CarterRichard Camicioli, Pamela Andrews, Magali Fernandez, Jean Hubble, Carson Reider, Ali Rajput, Alex Rajput, Theresa Shirley, Michael Panisset, Jean Hall, Tilak Mendis, David A. Grimes, Peggy Gray, Carmen Serrano Ramos, Sandra Roque, Stephen Reich, Becky Dunlop, Robert Hauser, Juan Sanchez-Ramos, Theresa Zesiewicz, Holly Delgado, Joseph Friedman, Hubert Fernandez, Margaret Lannon, Lauren Seeberger, Christopher O'Brien, Deborah Judd, Lawrence Elmer, Kathy Davis, Deborah Fontaine, Ronald Pfeiffer, Brenda Pfeiffer, Michael Aminoff, Mariann DiMinno, Daniel Truong, Mayank Pathak, Anhoa Tran, Robert Rodnitzky, Judith Dobson, Rajesh Pahwa, Stephanie Thomas, Danna Jennings, Kenneth Marek, Susan Mendick, Juliette Harris, William Weiner, Roger Kurlan, Debra Berry, Peter Lewitt, Maryan DeAngelis, Paul Tuite, Robyn Schacherer, Wayne Martin, Marguerite Wieler, Bala Manyam, Patricia Simpson, John Bertoni, Carolyn Peterson, Mark F. Gordon, Joanna Hamann, Joseph Jankovic, Christine Hunter, Stewart Factor, Sharon Evans, Anette Nieves, Julie So, Mark Stacy, Kelli Williamson, Francis Walker, Victoria Hunt, Un Jung Kang, Shirley Uy, Karen Bindauer, Jeannine Petit, David Simon, Lisa Scollins, Rachel Saunders Pullman, Karyn Boyer, Paul Gordon

Research output: Contribution to journalArticle

178 Scopus citations

Abstract

Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations. Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset ≤550 years) or positive lod score with a marker in intron 7 of the parkin gene. Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34%) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86%) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene. Conclusions: Mutations in the parkin gene occur among individuals with PD with an older age at onset (≥60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.

Original languageEnglish (US)
Pages (from-to)796-801
Number of pages6
JournalNeurology
Volume60
Issue number5
DOIs
StatePublished - Mar 11 2003

ASJC Scopus subject areas

  • Clinical Neurology

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    Foroud, T., Uniacke, S. K., Liu, L., Pankratz, N., Rudolph, A., Halter, C., Shults, C., Marder, K., Conneally, P. M., Nichols, W. C., Golbe, L., Koller, W., Lyons, K., Marshall, F., Oakes, D., Shinaman, A., Siemers, E., Wojcieszek, J., Belden, J., ... Gordon, P. (2003). Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology, 60(5), 796-801. https://doi.org/10.1212/01.WNL.0000049470.00180.07